The application of gene therapy in animal models of autoimmune disease will address questions relevant to autoimmune diseases and the alteration of immune responses. Meaningful T-cell gene therapy investigative approaches in animal models of autoimmune disease have been limited by the inability to efficiently transduce murine T cells. Work over the past 1.5 years in the Fathman laboratory has resulted in efficient retroviral transduction of antigen-reactive murine T cells. Furthermore, characterization of the transduced T cells has provided critical insight needed to begin gene therapy studies in animal models of autoimmune disease. This proposal will use antigen-specific retrovirally-modified T cells to locally deliver anti-inflammatory proteins to the site of tissue inflammation. The results from these studies will provide insight into disease pathogenesis, the ability to locally deliver disease-modifying proteins with autoantigen-reactive T cells, and the ability to alter immune responses. The findings from this work will have important implications for the future of gene therapy in human diseases that are the result of aberrant immune responses, i.e. autoimmune diseases and allergic diseases. The Principal Investigator, Dr. Christine Seroogy, is trained in pediatric allergy/immunology and is committed to a career in academic medicine. Previous research experience has provided the foundation for continuing along this career path. Dr. Seroogy joined the Fathman laboratory at Stanford University 1.5 years ago. Since that time she has acquired new skills in cellular immunology and gene therapy. Additional years of training, provided by the MCSDA, will allow her to develop into an independent investigator.